Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
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PMID:Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC. 1452 Apr 30

Tumors expressing a high level of certain types of tumor-associated carbohydrate antigens (TACAs) exhibit greater metastasis and progression than those expressing low level of TACAs, as reflected in decreased patient survival rate. Well-documented examples of such TACAs are: (i) H/Le(y)/Le(a) in primary non-small cell lung carcinoma; (ii) sialyl-Le(x) (SLe(x)) and sialyl-Le(a) (SLe(a)) in various types of cancer; (iii) Tn and sialyl-Tn in colorectal, lung, breast, and many other cancers; (iv) GM2, GD2, and GD3 gangliosides in neuroectodermal tumors (melanoma and neuroblastoma); (v) globo-H in breast, ovarian, and prostate cancer; (vi) disialylgalactosylgloboside in renal cell carcinoma. Some glycosylations and TACAs suppress invasiveness and metastatic potential. Well-documented examples are: (i) blood group A antigen in primary lung carcinoma; (ii) bisecting beta1 --> 4GlcNAc of N-linked structure in melanoma and other cancers; (iii) galactosylgloboside (GalGb4) in seminoma. The biochemical mechanisms by which the above glycosylation changes promote or suppress tumor metastasis and invasion are mostly unknown. A few exceptional cases in which we have some knowledge are: (i) SLe(x) and SLe(a) function as E-selectin epitopes promoting tumor cell interaction with endothelial cells; (ii) some tumor cells interact through binding of TACA to specific proteins other than selectin, or to specific carbohydrate expressed on endothelial cells or other target cells (carbohydrate-carbohydrate interaction); (iii) functional modification of adhesive receptor (integrin, cadherin, CD44) by glycosylation. So far, a few successful cases of anti-cancer vaccine in clinical trials have been reported, employing TACAs whose expression enhances malignancy. Examples are STn for suppression of breast cancer, GM2 and GD3 for melanoma, and globo-H for prostate cancer. Vaccine development canbe extended using other TACAs, with the following criteria for success: (i) the antigen is expressed highly on tumor cells; (ii) high antibody production depending on two factors: (a) clustering of antigen used in vaccine; (b) choice of appropriate carrier protein or lipid; (iii) high T cell response depending on choice of appropriate carrier protein or lipid; (iv) expression of the same antigen in normal epithelial tissues (e.g., renal, intestinal, colorectal) may not pose a major obstacle, i.e., these tissues are not damaged during immune response. Idiotypic anti-carbohydrate antibodies that mimic the surface profile of carbohydrate antigens, when administered to patients, elicit anti-carbohydrate antibody response, thus providing an effect similar to that of TACAs for suppression of tumor progression. An extension of this idea is the use of peptide mimetics of TACAs, based on phage display random peptide library. Although examples are so far highly limited, use of such "mimotopes" as immunogens may overcome the weak immunogenicity of TACAs in general.
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PMID:Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. 1453 9

We investigated the biologic meaning of tumor-associated macrophages (TAM) in renal cell carcinoma (RCC). The study group comprised of 83 patients with RCC. TAM was isolated by plastic adherence following enzymatic digestion of surgically removed tumor tissues. In some of the patients, monocytes were also isolated from peripheral blood mononuclear cells by plastic adherence. When TAM and monocytes were compared in the same patients, TAM produced interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) without lipopolysaccharide (LPS) stimulation, while monocytes hardly produced IL-6, TNFalpha and IL-1beta without LPS stimulation. However, with LPS stimulation, monocytes produced more IL-6, TNFalpha and IL-1beta than TAM. In stage T1 RCC patients, there was a significant positive correlation between TNFalpha production of TAM and tumor size. In order to investigate the effects of TAM on cancer cells, TAM was co-cultured with A498, K562 and in some cases, with short-term established RCC lines for 96 h. As a result, TAM largely enhanced cell proliferation. These results suggested that TAM may play an important role in certain steps of tumor progression.
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PMID:Role of tumor-associated macrophages in renal cell carcinoma. 1453 6

Previous studies indicate that the nonclassical class I HLA-G antigen, whose physiologic expression is mainly restricted to placenta, is upregulated in melanoma, renal carcinoma, lung carcinoma, glioblastoma and ovarian carcinoma, where its inhibitory effect on cytotoxic effector cells function is thought to participate in immune evasion by tumor cells. To define whether this expression was a specific feature of melanocytic malignant transformation, 174 paraffin-embedded melanocytic lesions including naevi, lentigo, primary and metastatic melanomas were analyzed for HLA-G and other HLA class I and class II antigen expression. HLA-G antigen expression in melanocytic cells was found to be significantly higher (p < 0.0003) in melanoma (22/79, 28%) than in naevi (1/70, 1.4%), suggesting that upregulation of HLA-G is associated with malignant transformation in this cell type. Further identification of HLA-G antigen expression in inflammatory infiltrating cells results in an overall frequency of HLA-G expressing cells that is higher in melanoma (28/79, 35.5%) than in naevi (5/60, 8.3%) or lentigo (2/23, 8.7%). Upregulation of HLA-G or HLA class II molecules in melanocytic cells thus appears as a better predictor of malignancy than classical HLA class I antigen defects, which are often described as an important mechanism used by tumor cells to evade immune surveillance. Furthermore, HLA-G expression was electively found in lesions that exhibited a high inflammatory infiltrate as well as in patients displaying HLA-A1 genotype. These findings may provide new insights in the comprehension of tumor progression and design of therapeutic approaches aimed at enhancing antitumor immune responses in melanoma patients.
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PMID:Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype. 1463 10

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.
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PMID:Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies. 1475 78

A 69-year-old woman visited a hospital with a complaint of left abdominal dull pain. A computed tomographic scan demonstrated a large tumor with central necrosis in the left retroperitoneum, and an angiography revealed hypervascular tumor which was fed from splenic, left renal, left gastric and left colic arteries. Renal cell carcinoma with extrarenal progression was pre-operatively suspected, and a resection was attempted. However, since the celiac artery was involved in the tumor, only a biopsy was performed. The histopathological finding of the biopsy specimen was a plasmacytoma. A combination of chemotherapy and radiation therapy resulted in a marked reduction of the tumor. There was no evidence of tumor progression one year after the chemotherapy.
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PMID:[A case of retroperitoneal extramedullary plasmacytoma]. 1497 56

Patients with renal cell carcinoma (RCC) were examined by the chemiluminescent analysis before and after surgery. The cells of subjects with the discussed pathology were found to be in the state of functionally metabolic misbalance, i.e. an increased initial level of the synthesis of active oxygen with a relatively reduced cell reactivity when additionally stimulated. Such specificity of neutrophil granulocytes of peripheral blood is more pronounced in RCC patients after surgery. Supposedly, the above phenomenon is preconditioned by a lack of metabolic reserves that could provide an adequate functional response to extra stimulation and it develops due to a prolonged tumor progression and stress brought about by surgical intervention.
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PMID:[Comparative analysis of the functional activity of neutrophil granulocytes from blood of patients with renal cell carcinoma before and after the surgical treatment]. 1502 12

Bevacizumab (Avastin; Genentech, Inc.; South San Francisco, CA) is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, a key regulator of tumor angiogenesis. Bevacizumab demonstrated potent antitumor activity in preclinical models and has also shown biologic activity and clinical benefit in clinical studies. Notably, a randomized, placebo-controlled phase II trial in renal cell carcinoma demonstrated a significantly longer time to tumor progression with bevacizumab monotherapy. Furthermore, in a phase III trial for untreated advanced colorectal cancer, the addition of bevacizumab to chemotherapy led to significantly longer overall survival and progression-free survival times than chemotherapy alone. The clinical development of bevacizumab has been expanded to include confirmatory phase III trials and exploratory phase II trials in a variety of solid tumors and hematologic malignancies. Treatment regimens being examined include bevacizumab alone and in combination with conventional chemotherapy, radiation, immune therapy, and biologically targeted agents.
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PMID:Expanding the clinical development of bevacizumab. 1517 13

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.
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PMID:Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity. 1522 Sep 55

Therapy of metastasized renal cell carcinoma is based on systemic immunotherapeutic strategies, if surgical resection is not possible. The costs of inhalative Interleukin-2 therapy in case of pulmonary metastases as off-label-use are not accepted by compulsory health insurance yet.We report on a female patient with pulmonary metastasized renal cell carcinoma who had tumor progression after immunochemotherapy that followed complete response after inhalative therapy with Interleukin-2.
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PMID:[Complete remission of pulmonary metastasis from renal cell carcinoma through inhalation therapy with Interleukin-2 after unsuccessful systemic immunochemotherapy]. 1537 56


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